Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Dec 4;146(48):32912-32918.
doi: 10.1021/jacs.4c11315. Epub 2024 Nov 21.

DNA-Regulated Multi-Protein Complement Control

Yinglun Ma  1   2 , Peter H Winegar  1   2 , C Adrian Figg  1   2 , Namrata Ramani  3   2 , Alex J Anderson  1   2 , Kathleen Ngo  1   2 , John F Ahrens  4   2 , Nikhil S Chellam  4   2 , Young Jun Kim  5   2 , Chad A Mirkin  1   3   4   5   2
Affiliations

DNA-Regulated Multi-Protein Complement Control

Yinglun Ma et al. J Am Chem Soc. .

Abstract

In nature, the interactions between proteins and their complements/substrates can dictate complex functions. Herein, we explore how DNA on nucleic acid modified proteins can be used as scaffolds to deliberately control interactions with a peptide complement (by adjusting length, sequence, and rigidity). As model systems, split GFPs were covalently connected through DNA scaffolds (36-58 bp). Increasing the length or decreasing the rigidity of the DNA scaffold (through removal of the duplex) increases the extent of intramolecular protein binding (up to 7.5-fold) between these GFP fragments. Independent and dynamic control over functional outputs can also be regulated by DNA hybridization; a multi-protein (split CFP and YFP) architecture was synthesized and characterized by fluorescence. This ternary construct shows that DNA displacement strands in different stoichiometric ratios can be used deliberately to regulate competitive binding between two unique sets of proteins. These studies establish a foundation for creating new classes of biological machinery based upon the concept of DNA-regulated multi-protein complement control.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interests.

References

    1. Reichmann D; Rahat O; Cohen M; Neuvirth H; Schreiber G The molecular architecture of protein–protein binding sites. Curr. Opin. Struct. Biol 2007, 17 (1), 67–76 - PubMed
    1. Ahnert SE; Marsh JA; Hernández H; Robinson CV; Teichmann SA Principles of assembly reveal a periodic table of protein complexes. Science 2015, 350 (6266), aaa2245. - PubMed
    1. Luo Q; Hou C; Bai Y; Wang R; Liu J Protein Assembly: Versatile Approaches to Construct Highly Ordered Nanostructures. Chem. Rev 2016, 116 (22), 13571–13632 - PubMed
    1. Pieters BJGE; Van Eldijk MB; Nolte RJM; Mecinović J Natural supramolecular protein assemblies. Chem. Soc. Rev 2016, 45 (1), 24–39 - PubMed
    1. Zhu J; Avakyan N; Kakkis A; Hoffnagle AM; Han K; Li Y; Zhang Z; Choi TS; Na Y; Yu C-J; et al. Protein assembly by design. Chem. Rev 2021, 121 (22), 13701–13796 - PMC - PubMed

MeSH terms

LinkOut - more resources